Lead Exposure: Pregnancy - MotherToBaby

Lead Exposure:Pregnancy & Beyond

Presented by:

Steve Lamm, MD, Georgetown University, MotherToBaby/Organization of Teratology Information Specialists memberClaire Coles, PhD, Emory University, MotherToBaby Georgia & PEHSU Region 4 Robert Geller, MD, Emory University, PEHSU Region 4Richard K. Miller, PhD, University of Rochester Medical Center, MotherToBaby UR Medicine

Hosted by the National Society of Genetic Counselors

Overview

by Steven H. Lamm, MD, DTPH

Member of MotherToBaby, a service of the Organization of

Teratology Information Specialists (OTIS) & The Teratology Society;

also, Department of Pediatrics (Epidemiology)

Georgetown University School of Medicine

(202) 333-2364

CDC Recommendations and Public Health Approach

Lead has been

recognized as a

neurotoxin since the

times of the Romans.

Its modern regulation in

the United States goes

back fifty years to the

early 1970’s with reduction of lead in

Paint, Gasoline, and

Infant Formula.

Lead in Infant Formulas – Knowledge does bring Response

Infant formula is a specific lead

exposure that is unique to infants.

1971 levels indicated that the

average newborn received its

maximum permitted lead

exposure from its formula alone.

Note the rapid reduction of lead

levels in infant formulas by 1972-

73 after the industry was notified

about lead problem.

Common External Sources of Exposure

Common

Indoor Dust and Paint

Renovations

Drinking Water

Soil

Occupational

Hobbies

Cosmetics

Foreign medicines

Glazed pottery

Drinking Water

Current Lead Regulations

Environmental

Ambient air 0.15 ug/m3

Lead paint 90 ppm (mg/L)

Painted surfaces 1 ug/cm2 (XRF)

Floor – Screen 25 ug/ft2

Risk assessment 40 ug/ft2

Playground soil 400 ppb (ug/gm)

Drinking water 15 ppb in <10%

Add NIOSH figure

Internal Source of Exposure

Over 90% of lead in the adult is stored in bone.

Pregnancy and Lactation are both associated with increased bone turnover, and that means release of

bone lead to increase blood lead.

Thus, lead sources can be either endogenous (internal) or

exogenous (external) or both.

Lead levels in Women (15-49 years)

Blood lead levels for

WCBA have dropped

remarkably in the past

35 years.

It appears that what

was the LCB in 1976-80

was the UCB in 2003-06.

5 μg/dL is today about

the 99% level for WCBA.

Current Reference level is BLL < 5 μg/dL

CDC - “A BLL >= 5 μg/dL in a pregnant woman indicates that she

has, or has recently had, exposure to lead well above that for most

women of child-bearing age in the US population.” [CDC, 2010,

page 52]

CDC is considering lowering the reference level to 3.5 μg/dl.

Algorithms for Response

Pregnancy

Test All,

If BLL < 5 μg/dL, Explain.

If BLL > 5 μg/dL, Explain.

Then – Retest in 1 month, find source

and isolate from it.

If BLL > 45 μg/dL, retest in 24 hrs.

Newborn

If mother BLL > 5 μg/dL, test at birth (umbilical or

venous).

If neonate BLL > 45 μg/dL, retest and get

immediate consult.

If neonate BLL 25-44 μg/dL, retest in 2 weeks

and get consult if not reduced.

If neonate BLL 5-24 μg/dL, retest in 1 month.

Breast feeding

Current recommendation – Continue if maternal BLL < 40 μg/dL

(Subject to change) and infant BLL < 5 ug/dL.

Benefit exceeds Risk.

Discontinue if maternal BLL > 20 μg/dL, infant BLL > 5 μg/dL and

not falling.

Consider endogenous lead source from mobilization of bone

lead.

References

Ettinger 2010. CDC Guidelines for the Identification and Management of Lead Exposure in Pregnant and Lactating Women. US DHHS Atlanta, Nov 2010. (302 pp)

CDC 2012. ACCLPP Report – Low Level Lead Exposure Harms Children: A Renewed Call for Primary Prevention. Jan 4, 2012. (65 pp).

AAP 2016. Prevention of Childhood Lead Toxicity. Pediatrics July 20, 138(1), e20161493 (17 pp).

MtB 2016. Questions and Answer on Lead during Pregnancy or Lactation. [Website]

MTB 2016. Fact Sheet on Lead @ mothertobaby.org

Neurobehavioral Effects of

Lead

by Claire D. Coles, PHD

Emory University

MotherToBaby Georgia

PEHSU Region 4

Lead

Heavy Metal.

Found in soil, air, included in gasoline, paint

Problems first noted historically

ug/dL (micrograms of lead per deciliter of blood)-reference level= 5ug/dL (CDC, 2016)

Substantial reduction in environmental lead levels in last 40 years.

Studied comprehensively

Effects of High Lead Exposure on

DevelopmentHistorically, lead toxicity associated with fatigue, irritability, mental illness,

decreased fertility, death.

Chronic exposure could produce neurotoxicity with intellectual disability

(“IQ”), learning deficits, and behavioral problems.

Needleman (1974) found an inverse relationship between lead in children’s

teeth and IQ as well as increased “nonadaptive classroom behavior” in

such children.

“ADHD”-like behaviors are greater in individuals with lead exposure-that is,

impulsive behavior, lack of cognitive behavioral control. (Winneke, 2011)

The Lead and Development

Controversies

Everyone agrees that high lead levels are bad, but is there an effect on Cognition of lead levels at less than 5 to 10 ug/dL?

Is it enough to test global IQ, or should other measures be used?

Is prenatal or postnatal lead exposure more damaging to subsequent child development?

Is behavior (that is to say, externalizing behavior and delinquency) affected by lead exposure?

Prenatal vs Postnatal Lead Exposure

and Development?

Questions about the relative risk of prenatal and postnatal exposure.

In general, the risk appears to be higher when exposure is postnatal. Children can

ingest more lead directly.

There appear to be some risks associated with prenatal exposure at various levels

and with breast feeding when maternal levels are greater than 20 ug/dl.

Neonates with elevated umbilical cord blood (>10 ug/dL) showed disturbance in arousal

and sleep.(Mamtani, et al, 2008)

Later in infancy, the same infants had lower scores on the Bayley Mental Development

Index at six months (MDI) (Al-Saleh, et al, 2009)

Lead can in breast milk (Ettinger, et al, 2004) but breast feeding is recommended unless

maternal levels are high.

Lead: Effects on Child Development

Meta-analysis of 26 epidemiological studies* found:

Moderate to high blood-lead levels (30-40 ug/dL) affect cognitive functioning (IQ) and ADHD

Lower level lead associated with small IQ (global) deficits (1-2 pts)

Unclear if levels as low as 5ug/dl cause risk for behavior or cognition in given individuals

Many confounders and effect modifiers must be considered

Socioeconomic Status (SES) (e.g., Poverty)

Reverse causality (e.g., Impulsivity)

Caregiving styles and factors (e.g., breast feeding)

Other toxins and teratogens (e.g., substance abuse)

Nutrition (e.g., iron deficiency)

*Pocock, et al (1994) Brit Med J, 1189-1196

Winneke, G (2011) Developmental aspects of environmental neurotoxicology: Lessons from lead and polychlorinated biphenyls. J. Neurological Sciences 308, 9-15

Experimental Studies of Lead Exposure

and Child Development

Motor Skills impaired during infancy/preschool

BPb associated with fine motor functions when confounders controlled.

Gross motor skills unaffected.

IQ in school aged children (4 to 8 years)-Several IQ points with low lead

levels.

Perceptual/Motor skills ; affected more than Language.

Effect Modification

(Boston Prospective Study)

122

125

110

115

110111

100

105

110

115

120

125

130

Low Mid High

High SES Low SeS

< 3 ug/dl 3-10 ug/dl 10-25 ug/dl

Bayley

Mental

Development

Index at 24

months

Cord Blood Lead Category

Bellinger et al. (1988) < 3, 3-<10, 10-<25 ug/dl. Conclusion: Early postnatal BLL 10-25 ug/dl assoc c lower MDI but only for low SES.

Source:

Canfield, Henderson, et al. (2003) New Engl J Med, 1517-1526

IQ at 5 years

and Blood

Lead: The Low

Lead

Controversy

Lead Exposure and Behavior Problems ADHD symptoms appear to be common in a number of studies and include:

hyperactivity, impulse disinhibition, distractibility, and conduct problems. (Braun, et

al. 2006; Nigg, et al, 2010; Wang, et al., 2008).

Evidence includes both behavioral surveys and experimental paradigms. (Minder

et al., 1994; Chido, et al, 2007)

Behavior problems were noted by Cincinnati Lead Study (1979-1985) (Dietrich, et al,

2001)

Longitudinal Sample Reassessed at X=15.6 years

92% African-American, low SES

Higher levels of self-reported delinquent behavior in adolescence associated with

BPb levels > 15 ug/dl at 6.5 yrs.

Not all environmental factors controlled.

Both prenatal and postnatal lead exposure affected outcomes

Treatment for Elevated Body

Lead Levels

by Robert J. Geller, MD

Emory University

PEHSU Region 4

Lead Poisoning – What to Do?

Terminate exposure to further lead

Abate housing

Lead paint

Lead plumbing

Renovate safely

Avoid leaded pottery for cooking / eating

Avoid ethnic remedies that contain lead

Interventions for the Individual

Early detection

Screening questions and blood levels

Supportive care

Early intervention programs have been proven to mitigate lead-driven disabilities

Symptom- based monitoring and treatment

Hypertension, for example

Chelation

Natural History of Human Lead Body

Burden

Roberts JR et al. Clin Toxicol 2001; 39: 153-160.

Lead Poisoning – What to Do?

The real question should be, “What can we do that makes a difference?”

Elevated Lead Levels

Optimal = 0

Current US Population average ≈ 2 µg/dL

CDC Intervention Level = 5 µg/dL

Chelation Level ?

One chelator’s FDA labeling uses level > 45 µg/dL

Initial Management

Eliminate further exposure

Confirm level as appropriate

Supplement dietary calcium and iron

Recheck level in an appropriate time frame

Lead Poisoning – What to Do Next?

Who should we chelate?

Data is limited

TLC trial – Newark, NY, Baltimore, 1993-2000

Double blind controlled study

Attempted to address the environment and provide nutritional supplements

Didn’t abate new residences after patients moved

TLC

TLC Outcomes

TLC Outcomes - 2

Study not intended to address subgroup analyses

No difference generated in post-hoc analyses between children chelated

below age 2 and after age 2, but power insufficient to decisively conclude

this

Personal communication, Walter Rogan, 2/29/12

What about other chelators?

IV = Calcium disodium EDTA

IM = BAL (dimercaprol)

Oral

DMPS

FDA approved in US for compounding use only

Penicillamine

Not FDA approved for lead chelation

Lead Exposures During Pregnancy:

Exposure and Remediation

Richard K. Miller, PhD, ATS

Director, MotherToBaby UR Medicine

Finger Lakes Children’s Environmental Health Center

Professor of Obstetrics/Gynecology, of Environmental Medicine,

of Pathology and Clinical Laboratory Medicine

University of Rochester School of Medicine and Dentistry,

and Teratology Society member

[email protected]

J Schneyer, MB Bell, Reuters, June 9, 2016

Mandatory

Lead Screening

Evaluation

In Pregnant Women

Lead Screening and Blood Testing

Experience in New York State Since 1995 -

Actions and Interventions

• Mandatory Lead Screening at 1st Prenatal Visit

• Follow up with Blood Lead Level Testing (BLL)

• Refer to Teratogen Information Services; County Dept of Health

• Follow-up with monthly BLL

• Interventions – Calcium, Iron, Vitamin C - Last resort -Chelation

• EXPERIENCE - Test all women in first trimester for Lead exposure

• Inspect all rental properties and require Certificate of

Occupancy (Coalition to Prevent Lead Poisoning, Rochester,

New York)

http://www.letsmakeleadhistory.org/https://www.health.ny.gov/environmental/lead/exposure/childhood/finalplantoc.htmhttp://www.cdc.gov/nceh/lead/publications/leadandpregnancy2010.pdf

Maternal Blood Lead During Pregnancy

0

10

20

30

40

50

60

70

0 10 20 30 40 50

Weeks

Blo

od

Lead

(u

g/d

l)

KXRF

Calcium

Supplements

Calcium & Vitamin CSupplements

Ca- Gulson et al. Environ Hlth Persp 112:1499, 04

Weeks

(Miller, unpublished)

Lead in Bone> 95% of the body burden of lead is in the skeleton.

Half-life of Lead in bone is 20-30 years.

Lead is released from bone during pregnancy at

increased rate.

1st trimester 2nd trimester 3rd trimester

Blood Lead

(µg/dl)

Calcium Supplemented

Calcium Deficient

Increased Calcium Demand

in 3rd Trimester Increases

Bone Lead Resorption

Derived from: Gulson et al.

J Lab Clin Med 1999;134:631-6403

10

Experience for MotherToBaby UR Medicine, 2016

TOP TEN Elevated Blood Lead in Pregnant Women –

1. Medicines – Ayurvedic Medicines (imported)

2. Remodeling/Repair Home - Apartment

3. Workplace – Electronics/Auto Repair/ Ceramic

Industry

4. Cosmetics – Eye Shadow (imported)

5. Ethnic Imported Foods – Salsa – Candies/Clay Pots

6. Hair Dyes - (imported)

7. Gun Shot Fragments –

8. Hobbies – Metal Work; Jewelry Making

9. Water Consumption – Drinking Coolers

10. Urine Drinking

TOP TEN - Elevated Blood Lead in Pregnant Women –

(MOST DIFFICULT TO IDENTIFY)

1. Urine Drinking



4. Ethnic Foods – Salsa (imported), Candies


6. Hobbies – metal work, jewelry making

7. Workplace – Electronics/Auto Repair

Ceramics Industry/ Bridge Repair


9. Remodeling/Repair Home - Apartment

10. Gun Shot Fragments Experience for MotherToBaby UR Medicine, 2016

TOP TEN - Elevated Blood Lead in Pregnant Women –

(MOST DIFFICULT To REMEDIATE)

1. Gun Shots Fragments


3. Workplace – Electronics/Auto Repair

4. Workplace - Ceramics Industry/ Bridge Repair


6. Ethnic Imported Foods – Salsa – Candies/Clay pots

7. Remodeling/Repair Home/ Apartment



10. Urine Drinking

Experience for MotherToBaby UR Medicine, 2016

Lead Exposures in Pregnant Women –KEYS TO SUCCESS

1. PREVENTION - Certificate of Occupancy for every rental property which

must include a lead inspection certification.

2. LEAD TESTING of pregnant women in FIRST Trimester (Not just Screening)

3. Engage Patient and her Physician – detailed history and repeat follow up

(including family members if at risk)

4. REPEAT BLOOD LEAD TESTING MONTHLY WHEN ELEVATED

5. INTERVENTIONS – Removal; Therapy (Calcium, Iron, Vitamin C); Chelation

6. Work closely with Local and State Departments of Health

7. Workplace – Work with employer and patient – for testing and actions to

remove patient from workplace exposures (verify new area is lead free).

Assist Workplace with recommendations for remediation.

8. Eliminating residential source of Lead - Remodeling/Repair Home/

Apartment; Home inspections by Certified Lead Inspectors

9. Water Consumption; Behavior modification for Ethnic Imported Foods –

Salsa – Candies in clay pots; Urine Drinking; Hair Dyes (Imported)

















































































































































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Lead Exposure: Pregnancy - MotherToBaby